Efficacy and Safety of Dovitinib in Patients With Gastrointestinal Stromal Tumors Refractory and/or Intolerant to Imatinib

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39 Patients enrolled. One patient had a protocol deviation which excluded him from the Full Analysis Set.

Arm/Group Title

Dovitinib

Arm/Group Description

Patients received Dovitinib (TKI258...

Arm/Group Description

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Baseline Participants

38

Baseline Analysis Population Description

...

Baseline Analysis Population Description

Full Analysis Set - All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

DCR is defined as the proportion of patients with a best overall respo...

Description

DCR is defined as the proportion of patients with a best overall response of Complete Responses (CR), Partial Response (PR) and Stable Disease (SD) at 12 weeks according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

Time Frame

12 Weeks

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: all subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Participants Analyzed

38

Measure Type: NumberNumber (90% Confidence Interval)

Unit of Measure: Percentage of Participants

52.6

(38.2 to 66.7)

2.Secondary Outcome

Title

Progression-free Survival (PFS) of Patients Treated With Dovitinib

Description

The PFS duration: time from entry into the study to the date of the fi...

Description

The PFS duration: time from entry into the study to the date of the first documented progression (assessed using conventional RECIST (version 1.1) or death due to any cause. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time Frame

9 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Participants Analyzed

38

Median (90% Confidence Interval)

Unit of Measure: Days

141

(86.0 to 225.0)

3.Secondary Outcome

Title

Time to Treatment Failure (TTF)of Patients Treated With Dovitinib

Description

TTF: the date of entry into the study to the earliest date of the firs...

Description

TTF: the date of entry into the study to the earliest date of the first objective tumor progression, date of death due to any cause, or date of discontinuation due to reasons other than 'Protocol deviation' or 'Administrative problems'.

Time Frame

9 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Participants Analyzed

38

Median (95% Confidence Interval)

Unit of Measure: Days

122.0

(81.0 to 223.0)

4.Secondary Outcome

Title

Duration of Response or Stable Disease (SD)

Description

Duration of response or SD: time from date of entry into study to earl...

Description

Duration of response or SD: time from date of entry into study to earliest date of first objective tumor progression or death. DCR is defined as proportion of patients with best overall response of CR, PR and SD at 12 weeks according to RECIST (version 1.1). CR: Disappearance of all non-nodal target lesions. Any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1; PR: At least a 30% decrease in sum of diameter of all target lesions, taking as reference the baseline sum of diameters. PD: At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

Time Frame

9 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Participants Analyzed

38

Mean (Standard Deviation)

Unit of Measure: Days

193.2
(117.78)

5.Secondary Outcome

Title

Time to Tumor Progression (TTP)of Patients Treated With Dovitinib

Description

TTP: time from the date of entry into the study to first documentation...

Description

TTP: time from the date of entry into the study to first documentation of tumor progression or death due to the underlying cancer. Progression is defined using Response Evaluation Criteria in Solid Tumors Criteria (RECIST v1.1), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

Time Frame

9 months

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Outcome Measure Description: ORR: proportion of patients whose best overall response is either complete response (CR) or partial response (PR) according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

Time Frame

Baseline, 12 weeks

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Participants Analyzed

38

Measure Type: NumberNumber (90% Confidence Interval)

Unit of Measure: Percentage of Participants

2.6

(0.1 to 11.9)

7.Secondary Outcome

Title

Overall Survival (OS) of Patients Treated With Dovitinib

Description

Outcome Measure Description: OS: time from the date of entry into the ...

Description

Outcome Measure Description: OS: time from the date of entry into the study to the date of death due to any cause. A patient who has not died by the date of the analysis cut-off would have the OS censored at the time of the last contact before the cut-off date.

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Overall Number of Participants Analyzed

38

Median (95% Confidence Interval)

Unit of Measure: Months

NA [1]

(NA to NA)

[1]

The median survival had not been reached

8.Secondary Outcome

Title

DCR (CR+PR+SD) at the End of Treatment

Description

DCR is defined as the proportion of patients with a best overall respo...

Description

DCR is defined as the proportion of patients with a best overall response of CR, PR and SD at the end of dovitinib treatment according to RECIST (version 1.1). Complete Response (CR): Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm 1;Partial Response (PR): At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm2. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.

Time Frame

Up to 9 months of estimated treatment

Outcome Measure Data Outcome Measure Data

Analysis Population Description

Analysis Population Description

Full Analysis Set: All subjects with histologically confirmed diagnosis of GIST who received at least one dose of study drug.

Arm/Group Title

Dovitinib

Arm/Group Description:

Patients received Dovitinib (TKI258...

Arm/Group Description:

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

Patients received Dovitinib (TKI258) on an outpatient basis at the dose of 500 mg qd for 5 days followed by 2 days off, every week for cycle of 4 weeks (28d) until disease progression, unacceptable toxicity, or consent withdrawal.

All-Cause Mortality

Dovitinib

Affected / at Risk (%)

Total

--/--

Serious Adverse Events Serious Adverse Events

Dovitinib

Affected / at Risk (%)

Total

16/39 (41.03%)

Blood and lymphatic system disorders

Anaemia † 1

1/39 (2.56%)

Leukopenia † 1

1/39 (2.56%)

Pancytopenia † 1

1/39 (2.56%)

Cardiac disorders

Cardiac arrest † 1

1/39 (2.56%)

Tachycardia † 1

1/39 (2.56%)

Gastrointestinal disorders

Abdominal pain † 1

1/39 (2.56%)

Abdominal pain upper † 1

1/39 (2.56%)

Ascites † 1

1/39 (2.56%)

Diarrhoea † 1

2/39 (5.13%)

Nausea † 1

1/39 (2.56%)

Peritoneal haemorrhage † 1

1/39 (2.56%)

Vomiting † 1

3/39 (7.69%)

General disorders

Asthenia † 1

1/39 (2.56%)

Fatigue † 1

4/39 (10.26%)

General physical health deterioration † 1

1/39 (2.56%)

Inflammation † 1

1/39 (2.56%)

Localised oedema † 1

1/39 (2.56%)

Mucosal dryness † 1

1/39 (2.56%)

Oedema peripheral † 1

1/39 (2.56%)

Systemic inflammatory response syndrome † 1

1/39 (2.56%)

Hepatobiliary disorders

Cholestasis † 1

1/39 (2.56%)

Infections and infestations

H1N1 influenza † 1

1/39 (2.56%)

Tracheobronchitis † 1

1/39 (2.56%)

Investigations

Red blood cell count decreased † 1

1/39 (2.56%)

Weight decreased † 1

1/39 (2.56%)

Metabolism and nutrition disorders

Decreased appetite † 1

2/39 (5.13%)

Dehydration † 1

1/39 (2.56%)

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Malignant melanoma † 1

1/39 (2.56%)

Prostate cancer † 1

1/39 (2.56%)

Nervous system disorders

Neuropathy peripheral † 1

1/39 (2.56%)

Paraesthesia † 1

1/39 (2.56%)

Psychiatric disorders

Mania † 1

1/39 (2.56%)

Respiratory, thoracic and mediastinal disorders

Chronic obstructive pulmonary disease † 1

1/39 (2.56%)

Dyspnoea † 1

1/39 (2.56%)

Hiccups † 1

1/39 (2.56%)

Lung disorder † 1

1/39 (2.56%)

Pulmonary embolism † 1

2/39 (5.13%)

Skin and subcutaneous tissue disorders

Toxic skin eruption † 1

1/39 (2.56%)

Vascular disorders

Aortic thrombosis † 1

1/39 (2.56%)

Phlebitis † 1

1/39 (2.56%)

†

Indicates events were collected by systematic assessment

1

Term from vocabulary, MedDRA

Other (Not Including Serious) Adverse Events Other (Not Including Serious) Adverse Events

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts
the PI's rights to discuss or publish trial results after the trial is completed.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.